A continuing set of experiments in man using marihuana or its constituents will attempt to elucidate the following areas of interest: a) Specific physiological and biochemical actions of THC will be looked at. The immediate goal will be to determine whether or not THC shares with some other hallucinogens an antidiuretic effect, and to determine its effect on the urinary excretion of the norepinephrine metabolite, MHPG. b) Identification of metabolites of marihuana in urine, looking for those whose urinary excretion has a time-course similar to that of the clinical span of action of the drug. So far three such potential markers have been found: THC itself, unconjugated THC-11-oic acid and dihydroxy alcohol forms of THC. c) Interactions of THC with other compounds,especially those which might relate to the mode of action of the drug. The first interaction of this type to be studied will be one between acetylcholine and THC, using two different sorts of cholinomimetic drugs. One will be a precursor of acetylcholine, choline; the other will be an anticholinesterase, tetrahydroaminacrin. d) Factors influencing the variable clinical responses to the drug will focus not on the set of subjects. e) Further exploration of therapeutic uses of marihuana or homologs of its components will look at the possible antiemetic action of a cannabinol derivative, nabilone. f) A new area of research will be the correlation of plasma concentrations of THC with clinical effects. An effort will be made to define a range of plasma concentrations associated with impaired psychomotor functions. Other studies may be done as various leads suggest.